Individuals with high level spinal cord injury (SCI) have limited options for assistive control of their environments due in part to limited signal diversity for computer interface of patients' volitional motor systems. The tongue, a motor system capable of executing diverse movements under voluntary control, is spared in patients with high SCI and is thus a natural substrate for computer interfacing in quadriplegics. We have developed the tongue drive system (TDS) to allow unencumbered translation of tongue movements in real time for computer interfacing via a titanium-encased magnet (Ti-Mag) affixed to the tongue. Despite our technological innovation, TDS application in humans is precluded by a lack of information on Ti-Mag implant bio-compatibility and safety. In Specific Aim 1, we test the effect of implant design (size, shape, surfacing) and location on implant migration and tissue reaction in a rabbit model with a scaled implant to more closely reflect implant/tongue ratio in humans. In Specific Aim 2, using optimal parameters defined in Specific Aim 1, we quantitatively assess the anatomical and molecular responses to Ti-Mag implantation and explantation. We additionally test for possible deficit of tongue function due to implantation and explantation by quantitatively assessing changes in tongue lick performance. In Specific Aim 3 we test anatomical, molecular and physiological responses to Ti-Mag implantation and explantation in the mini-pig using a device designed for human application. We hypothesize that implantation and explantation under optimized parameters will produce only minor and local tissue reaction (e.g., device encapsulation) and will not impair measureable tongue function. Demonstration of device biocompatibility and safety is requisite to direct testing in humans with quadriplegia.